Hostname: page-component-78c5997874-94fs2 Total loading time: 0 Render date: 2024-11-13T01:37:13.018Z Has data issue: false hasContentIssue false
  • English
  • Français

Non-syndromic hereditary sensorineural hearing loss: review of the genes involved

Published online by Cambridge University Press:  14 January 2014

F Stelma  and
M F Bhutta
F Stelma*
Affiliation:
MRC Harwell, Harwell Science and Innovation Campus, Didcot, UK Department of Otorhinolaryngology, University of Groningen, University Medical Centre Groningen, The Netherlands
M F Bhutta
Affiliation:
MRC Harwell, Harwell Science and Innovation Campus, Didcot, UK Nuffield Department of Surgical Sciences (University of Oxford) and Department of Otolaryngology Head and Neck Surgery, John Radcliffe Hospital, Oxford, UK
*
Address for correspondence: Dr F Stelma, MRC Harwell, Harwell Science and Innovation Campus, Didcot OX11 0RD, UK Fax: +44 (0) 1235 841172 E-mail: femkestelma@gmail.com
Get access Rights & Permissions [Opens in a new window]

Abstract

Background:

Hereditary sensorineural hearing loss is the most frequently occurring birth defect. It has profound effects for the individual and is a substantial burden on society. Insight into disease mechanisms can help to broaden therapeutic options and considerably lower lifetime social costs. In the past few decades, the identification of genes that can cause this type of hearing loss has developed rapidly.

Objective:

This paper provides a concise overview of the currently known genes involved in non-syndromic hereditary hearing loss and their function in the inner ear.

Keywords

Sensorineural Hearing LossEar, InnerAnatomyMutationsGenetic Research
Type
Review Articles
Information
The Journal of Laryngology & Otology , Volume 128 , Issue 1 , January 2014 , pp. 13 - 21
Copyright
Copyright © JLO (1984) Limited 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1White, KR. Early hearing detection and intervention programs: opportunities for genetic services. Am J Med Genet A 2004;130A:29–36Google Scholar
2Keren, R, Helfand, M, Homer, C, McPhillips, H, Lieu, TA. Projected cost-effectiveness of statewide universal newborn hearing screening. Pediatrics 2002;110:855–64CrossRefGoogle ScholarPubMed
3Smith, RJ, Bale, JF Jr, White, KR. Sensorineural hearing loss in children. Lancet 2005;365:879–90Google Scholar
4Morton, NE. Genetic epidemiology of hearing impairment. Ann N Y Acad Sci 1991;630:16–31Google Scholar
5Hilgert, N, Smith, RJ, Van Camp, G. Forty-six genes causing nonsyndromic hearing impairment: which ones should be analyzed in DNA diagnostics? Mutat Res 2009;681:189–96Google Scholar
6Pakdaman, MN, Herrmann, BS, Curtin, HD, Van Beek-King, J, Lee, DJ. Cochlear implantation in children with anomalous cochleovestibular anatomy: a systematic review. Otolaryngol Head Neck Surg 2012;146:180–90Google Scholar
7Black, J, Hickson, L, Black, B, Perry, C. Prognostic indicators in paediatric cochlear implant surgery: a systematic literature review. Cochlear Implants Int 2011;12:67–93Google Scholar
8Rance, G, Barker, EJ. Speech perception in children with auditory neuropathy/dyssynchrony managed with either hearing aids or cochlear implants. Otol Neurotol 2008;29:179–82CrossRefGoogle ScholarPubMed
9Breneman, AI, Gifford, RH, Dejong, MD. Cochlear implantation in children with auditory neuropathy spectrum disorder: long-term outcomes. J Am Acad Audiol 2012;23:5–17Google Scholar
10Akil, O, Seal, RP, Burke, K, Wang, C, Alemi, A, During, M et al. Restoration of hearing in the VGLUT3 knockout mouse using virally mediated gene therapy. Neuron 2012;75:283–93Google Scholar
11Lustig, LR, Akil, O. Cochlear gene therapy. Curr Opin Neurol 2012;25:57–60Google Scholar
12Dror, AA, Avraham, KB. Hearing loss: mechanisms revealed by genetics and cell biology. Annu Rev Genet 2009;43:411–37Google Scholar
13Hudspeth, AJ. How hearing happens. Neuron 1997;19:947–50Google Scholar
14Legan, PK, Lukashkina, VA, Goodyear, RJ, Lukashkin, AN, Verhoeven, K, Van Camp, G et al. A deafness mutation isolates a second role for the tectorial membrane in hearing. Nat Neurosci 2005;8:1035–42Google Scholar
15Brownell, WE, Bader, CR, Bertrand, D, de Ribaupierre, Y. Evoked mechanical responses of isolated cochlear outer hair cells. Science 1985;227:194–6Google Scholar
16Rzadzinska, AK, Schneider, ME, Davies, C, Riordan, GP, Kachar, B. An actin molecular treadmill and myosins maintain stereocilia functional architecture and self-renewal. J Cell Biol 2004;164:887–97Google Scholar
17van Wijk, E, Krieger, E, Kemperman, MH, De Leenheer, EM, Huygen, PL, Cremers, CW et al. A mutation in the gamma actin 1 (ACTG1) gene causes autosomal dominant hearing loss (DFNA20/26). J Med Genet 2003;40:879–84Google Scholar
18Zhu, M, Yang, T, Wei, S, DeWan, AT, Morell, RJ, Elfenbein, JL et al. Mutations in the gamma-actin gene (ACTG1) are associated with dominant progressive deafness (DFNA20/26). Am J Hum Genet 2003;73:1082–91CrossRefGoogle ScholarPubMed
19Lynch, ED, Lee, MK, Morrow, JE, Welcsh, PL, Leon, PE, King, MC. Nonsyndromic deafness DFNA1 associated with mutation of a human homolog of the Drosophila gene diaphanous. Science 1997;278:1315–18CrossRefGoogle ScholarPubMed
20Kitajiri, S, Sakamoto, T, Belyantseva, IA, Goodyear, RJ, Stepanyan, R, Fujiwara, I et al. Actin-bundling protein TRIOBP forms resilient rootlets of hair cell stereocilia essential for hearing. Cell 2010;141:786–98Google Scholar
21Riazuddin, S, Khan, SN, Ahmed, ZM, Ghosh, M, Caution, K, Nazli, S et al. Mutations in TRIOBP, which encodes a putative cytoskeletal-organizing protein, are associated with nonsyndromic recessive deafness. Am J Hum Genet 2006;78:137–43Google Scholar
22Shahin, H, Walsh, T, Sobe, T, Abu Sa'ed, J, Abu Rayan, A, Lynch, ED et al. Mutations in a novel isoform of TRIOBP that encodes a filamentous-actin binding protein are responsible for DFNB28 recessive nonsyndromic hearing loss. Am J Hum Genet 2006;78:144–52Google Scholar
23Rehman, AU, Morell, RJ, Belyantseva, IA, Khan, SY, Boger, ET, Shahzad, M et al. Targeted capture and next-generation sequencing identifies C9orf75, encoding taperin, as the mutated gene in nonsyndromic deafness DFNB79. Am J Hum Genet 2010;86:378–88Google Scholar
24Huebner, AK, Gandia, M, Frommolt, P, Maak, A, Wicklein, EM, Thiele, H et al. Nonsense mutations in SMPX, encoding a protein responsive to physical force, result in X-chromosomal hearing loss. Am J Hum Genet 2011;88:621–7Google Scholar
25Schraders, M, Haas, SA, Weegerink, NJ, Oostrik, J, Hu, H, Hoefsloot, LH et al. Next-generation sequencing identifies mutations of SMPX, which encodes the small muscle protein, X-linked, as a cause of progressive hearing impairment. Am J Hum Genet 2011;88:628–34Google Scholar
26Bartles, JR, Wierda, A, Zheng, L. Identification and characterization of espin, an actin-binding protein localized to the F-actin-rich junctional plaques of Sertoli cell ectoplasmic specializations. J Cell Sci 1996;109:1229–39Google Scholar
27Zheng, L, Sekerkova, G, Vranich, K, Tilney, LG, Mugnaini, E, Bartles, JR. The deaf jerker mouse has a mutation in the gene encoding the espin actin-bundling proteins of hair cell stereocilia and lacks espins. Cell 2000;102:377–85CrossRefGoogle Scholar
28Boulouiz, R, Li, Y, Soualhine, H, Abidi, O, Chafik, A, Nurnberg, G et al. A novel mutation in the Espin gene causes autosomal recessive nonsyndromic hearing loss but no apparent vestibular dysfunction in a Moroccan family. Am J Med Genet A 2008;146A:3086–9Google Scholar
29Naz, S, Griffith, AJ, Riazuddin, S, Hampton, LL, Battey, JF Jr, Khan, SN et al. Mutations of ESPN cause autosomal recessive deafness and vestibular dysfunction. J Med Genet 2004;41:591–5Google Scholar
30Donaudy, F, Zheng, L, Ficarella, R, Ballana, E, Carella, M, Melchionda, S et al. Espin gene (ESPN) mutations associated with autosomal dominant hearing loss cause defects in microvillar elongation or organisation. J Med Genet 2006;43:157–61CrossRefGoogle ScholarPubMed
31Pataky, F, Pironkova, R, Hudspeth, AJ. Radixin is a constituent of stereocilia in hair cells. Proc Natl Acad Sci U S A 2004;101:2601–6CrossRefGoogle ScholarPubMed
32Khan, SY, Ahmed, ZM, Shabbir, MI, Kitajiri, S, Kalsoom, S, Tasneem, S et al. Mutations of the RDX gene cause nonsyndromic hearing loss at the DFNB24 locus. Hum Mutat 2007;28:417–23Google Scholar
33Goodyear, RJ, Marcotti, W, Kros, CJ, Richardson, GP. Development and properties of stereociliary link types in hair cells of the mouse cochlea. J Comp Neurol 2005;485:75–85Google Scholar
34Mburu, P, Mustapha, M, Varela, A, Weil, D, El-Amraoui, A, Holme, RH et al. Defects in whirlin, a PDZ domain molecule involved in stereocilia elongation, cause deafness in the whirler mouse and families with DFNB31. Nat Genet 2003;34:421–8Google Scholar
35Ouyang, XM, Xia, XJ, Verpy, E, Du, LL, Pandya, A, Petit, C et al. Mutations in the alternatively spliced exons of USH1C cause non-syndromic recessive deafness. Hum Genet 2002;111:26–30Google Scholar
36Ahmed, ZM, Smith, TN, Riazuddin, S, Makishima, T, Ghosh, M, Bokhari, S et al. Nonsyndromic recessive deafness DFNB18 and Usher syndrome type IC are allelic mutations of USHIC. Hum Genet 2002;110:527–31Google Scholar
37Shabbir, MI, Ahmed, ZM, Khan, SY, Riazuddin, S, Waryah, AM, Khan, SN et al. Mutations of human TMHS cause recessively inherited non-syndromic hearing loss. J Med Genet 2006;43:634–40Google Scholar
38Schraders, M, Oostrik, J, Huygen, PL, Strom, TM, van Wijk, E, Kunst, HP et al. Mutations in PTPRQ are a cause of autosomal-recessive nonsyndromic hearing impairment DFNB84 and associated with vestibular dysfunction. Am J Hum Genet 2010;86:604–10Google Scholar
39Verpy, E, Masmoudi, S, Zwaenepoel, I, Leibovici, M, Hutchin, TP, Del Castillo, I et al. Mutations in a new gene encoding a protein of the hair bundle cause non-syndromic deafness at the DFNB16 locus. Nat Genet 2001;29:345–9Google Scholar
40Zheng, J, Miller, KK, Yang, T, Hildebrand, MS, Shearer, AE, DeLuca, AP et al. Carcinoembryonic antigen-related cell adhesion molecule 16 interacts with alpha-tectorin and is mutated in autosomal dominant hearing loss (DFNA4). Proc Natl Acad Sci U S A 2011;108:4218–23Google Scholar
41Zwaenepoel, I, Mustapha, M, Leibovici, M, Verpy, E, Goodyear, R, Liu, XZ et al. Otoancorin, an inner ear protein restricted to the interface between the apical surface of sensory epithelia and their overlying acellular gels, is defective in autosomal recessive deafness DFNB22. Proc Natl Acad Sci U S A 2002;99:6240–5Google Scholar
42Bork, JM, Peters, LM, Riazuddin, S, Bernstein, SL, Ahmed, ZM, Ness, SL et al. Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of the novel cadherin-like gene CDH23. Am J Hum Genet 2001;68:26–37Google Scholar
43Michalski, N, Michel, V, Caberlotto, E, Lefevre, GM, van Aken, AF, Tinevez, JY et al. Harmonin-b, an actin-binding scaffold protein, is involved in the adaptation of mechanoelectrical transduction by sensory hair cells. Pflugers Arch 2009;459:115–30CrossRefGoogle ScholarPubMed
44Michalski, N, Michel, V, Bahloul, A, Lefevre, G, Barral, J, Yagi, H et al. Molecular characterization of the ankle-link complex in cochlear hair cells and its role in the hair bundle functioning. J Neurosci 2007;27:6478–88Google Scholar
45Goodyear, RJ, Legan, PK, Wright, MB, Marcotti, W, Oganesian, A, Coats, SA et al. A receptor-like inositol lipid phosphatase is required for the maturation of developing cochlear hair bundles. J Neurosci 2003;23:9208–19Google Scholar
46Gillespie, PG, Dumont, RA, Kachar, B. Have we found the tip link, transduction channel, and gating spring of the hair cell? Curr Opin Neurobiol 2005;15:389–96Google Scholar
47Michel, V, Goodyear, RJ, Weil, D, Marcotti, W, Perfettini, I, Wolfrum, U et al. Cadherin 23 is a component of the transient lateral links in the developing hair bundles of cochlear sensory cells. Dev Biol 2005;280:281–94Google Scholar
48Kazmierczak, P, Sakaguchi, H, Tokita, J, Wilson-Kubalek, EM, Milligan, RA, Muller, U et al. Cadherin 23 and protocadherin 15 interact to form tip-link filaments in sensory hair cells. Nature 2007;449:87–91Google Scholar
49Xiong, W, Grillet, N, Elledge, HM, Wagner, TF, Zhao, B, Johnson, KR et al. TMHS is an integral component of the mechanotransduction machinery of cochlear hair cells. Cell 2012;151:1283–95Google Scholar
50Verpy, E, Leibovici, M, Michalski, N, Goodyear, RJ, Houdon, C, Weil, D et al. Stereocilin connects outer hair cell stereocilia to one another and to the tectorial membrane. J Comp Neurol 2011;519:194–210Google Scholar
51Friedman, LM, Dror, AA, Avraham, KB. Mouse models to study inner ear development and hereditary hearing loss. Int J Dev Biol 2007;51:609–31CrossRefGoogle ScholarPubMed
52Donaudy, F, Ferrara, A, Esposito, L, Hertzano, R, Ben-David, O, Bell, RE et al. Multiple mutations of MYO1A, a cochlear-expressed gene, in sensorineural hearing loss. Am J Hum Genet 2003;72:1571–7Google Scholar
53Walsh, T, Walsh, V, Vreugde, S, Hertzano, R, Shahin, H, Haika, S et al. From flies' eyes to our ears: mutations in a human class III myosin cause progressive nonsyndromic hearing loss DFNB30. Proc Natl Acad Sci U S A 2002;99:7518–23Google Scholar
54Melchionda, S, Ahituv, N, Bisceglia, L, Sobe, T, Glaser, F, Rabionet, R et al. MYO6, the human homologue of the gene responsible for deafness in Snell's waltzer mice, is mutated in autosomal dominant nonsyndromic hearing loss. Am J Hum Genet 2001;69:635–40Google Scholar
55Ahmed, ZM, Morell, RJ, Riazuddin, S, Gropman, A, Shaukat, S, Ahmad, MM et al. Mutations of MYO6 are associated with recessive deafness, DFNB37. Am J Hum Genet 2003;72:1315–22Google Scholar
56Liu, XZ, Walsh, J, Tamagawa, Y, Kitamura, K, Nishizawa, M, Steel, KP et al. Autosomal dominant non-syndromic deafness caused by a mutation in the myosin VIIA gene. Nat Genet 1997;17:268–9CrossRefGoogle ScholarPubMed
57Weil, D, Kussel, P, Blanchard, S, Levy, G, Levi-Acobas, F, Drira, M et al. The autosomal recessive isolated deafness, DFNB2, and the Usher 1B syndrome are allelic defects of the myosin-VIIA gene. Nat Genet 1997;16:191–3Google Scholar
58Lalwani, AK, Goldstein, JA, Kelley, MJ, Luxford, W, Castelein, CM, Mhatre, AN. Human nonsyndromic hereditary deafness DFNA17 is due to a mutation in nonmuscle myosin MYH9. Am J Hum Genet 2000;67:1121–8Google Scholar
59Donaudy, F, Snoeckx, R, Pfister, M, Zenner, HP, Blin, N, Di Stazio, M et al. Nonmuscle myosin heavy-chain gene MYH14 is expressed in cochlea and mutated in patients affected by autosomal dominant hearing impairment (DFNA4). Am J Hum Genet 2004;74:770–6CrossRefGoogle ScholarPubMed
60Wang, A, Liang, Y, Fridell, RA, Probst, FJ, Wilcox, ER, Touchman, JW et al. Association of unconventional myosin MYO15 mutations with human nonsyndromic deafness DFNB3. Science 1998;280:1447–51Google Scholar
61Heidrych, P, Zimmermann, U, Kuhn, S, Franz, C, Engel, J, Duncker, SV et al. Otoferlin interacts with myosin VI: implications for maintenance of the basolateral synaptic structure of the inner hair cell. Hum Mol Genet 2009;18:2779–90Google Scholar
62Yasunaga, S, Grati, M, Cohen-Salmon, M, El-Amraoui, A, Mustapha, M, Salem, N et al. A mutation in OTOF, encoding otoferlin, a FER-1-like protein, causes DFNB9, a nonsyndromic form of deafness. Nat Genet 1999;21:363–9Google Scholar
63Ruel, J, Emery, S, Nouvian, R, Bersot, T, Amilhon, B, Van Rybroek, JM et al. Impairment of SLC17A8 encoding vesicular glutamate transporter-3, VGLUT3, underlies nonsyndromic deafness DFNA25 and inner hair cell dysfunction in null mice. Am J Hum Genet 2008;83:278–92Google Scholar
64Seal, RP, Akil, O, Yi, E, Weber, CM, Grant, L, Yoo, J et al. Sensorineural deafness and seizures in mice lacking vesicular glutamate transporter 3. Neuron 2008;57:263–75Google Scholar
65Ben-Yosef, T, Belyantseva, IA, Saunders, TL, Hughes, ED, Kawamoto, K, Van Itallie, CM et al. Claudin 14 knockout mice, a model for autosomal recessive deafness DFNB29, are deaf due to cochlear hair cell degeneration. Hum Mol Genet 2003;12:2049–61Google Scholar
66Wilcox, ER, Burton, QL, Naz, S, Riazuddin, S, Smith, TN, Ploplis, B et al. Mutations in the gene encoding tight junction claudin-14 cause autosomal recessive deafness DFNB29. Cell 2001;104:165–72Google Scholar
67Riazuddin, S, Ahmed, ZM, Fanning, AS, Lagziel, A, Kitajiri, S, Ramzan, K et al. Tricellulin is a tight-junction protein necessary for hearing. Am J Hum Genet 2006;79:1040–51Google Scholar
68Walsh, T, Pierce, SB, Lenz, DR, Brownstein, Z, Dagan-Rosenfeld, O, Shahin, H et al. Genomic duplication and overexpression of TJP2/ZO-2 leads to altered expression of apoptosis genes in progressive nonsyndromic hearing loss DFNA51. Am J Hum Genet 2010;87:101–9Google Scholar
69Lenz, DR, Avraham, KB. Hereditary hearing loss: from human mutation to mechanism. Hear Res 2011;281:3–10Google Scholar
70Hoang Dinh, E, Ahmad, S, Chang, Q, Tang, W, Stong, B, Lin, X. Diverse deafness mechanisms of connexin mutations revealed by studies using in vitro approaches and mouse models. Brain Res 2009;1277:52–69Google Scholar
71Kelsell, DP, Dunlop, J, Stevens, HP, Lench, NJ, Liang, JN, Parry, G et al. Connexin 26 mutations in hereditary non-syndromic sensorineural deafness. Nature 1997;387:80–3Google Scholar
72Xia, JH, Liu, CY, Tang, BS, Pan, Q, Huang, L, Dai, HP et al. Mutations in the gene encoding gap junction protein beta-3 associated with autosomal dominant hearing impairment. Nat Genet 1998;20:370–3Google Scholar
73Liu, XZ, Xia, XJ, Xu, LR, Pandya, A, Liang, CY, Blanton, SH et al. Mutations in connexin 31 underlie recessive as well as dominant non-syndromic hearing loss. Hum Mol Genet 2000;9:63–7Google Scholar
74Grifa, A, Wagner, CA, D'Ambrosio, L, Melchionda, S, Bernardi, F, Lopez-Bigas, N et al. Mutations in GJB6 cause nonsyndromic autosomal dominant deafness at DFNA3 locus. Nat Genet 1999;23:16–18Google Scholar
75del Castillo, I, Villamar, M, Moreno-Pelayo, MA, del Castillo, FJ, Alvarez, A, Telleria, D et al. A deletion involving the connexin 30 gene in nonsyndromic hearing impairment. N Engl J Med 2002;346:243–9CrossRefGoogle ScholarPubMed
76Kubisch, C, Schroeder, BC, Friedrich, T, Lutjohann, B, El-Amraoui, A, Marlin, S et al. KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness. Cell 1999;96:437–46Google Scholar
77Heidenreich, M, Lechner, SG, Vardanyan, V, Wetzel, C, Cremers, CW, De Leenheer, EM et al. KCNQ4 K(+) channels tune mechanoreceptors for normal touch sensation in mouse and man. Nat Neurosci 2011;15:138–45CrossRefGoogle ScholarPubMed
78Schultz, JM, Yang, Y, Caride, AJ, Filoteo, AG, Penheiter, AR, Lagziel, A et al. Modification of human hearing loss by plasma-membrane calcium pump PMCA2. N Engl J Med 2005;352:1557–64Google Scholar
79Bortolozzi, M, Brini, M, Parkinson, N, Crispino, G, Scimemi, P, De Siati, RD et al. The novel PMCA2 pump mutation Tommy impairs cytosolic calcium clearance in hair cells and links to deafness in mice. J Biol Chem 2010;285:37693–703Google Scholar
80Riazuddin, S, Anwar, S, Fischer, M, Ahmed, ZM, Khan, SY, Janssen, AG et al. Molecular basis of DFNB73: mutations of BSND can cause nonsyndromic deafness or Bartter syndrome. Am J Hum Genet 2009;85:273–80CrossRefGoogle ScholarPubMed
81Li, XC, Everett, LA, Lalwani, AK, Desmukh, D, Friedman, TB, Green, ED et al. A mutation in PDS causes non-syndromic recessive deafness. Nat Genet 1998;18:215–17Google Scholar
82Everett, LA, Glaser, B, Beck, JC, Idol, JR, Buchs, A, Heyman, M et al. Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS). Nat Genet 1997;17:411–22Google Scholar
83Zheng, J, Shen, W, He, DZ, Long, KB, Madison, LD, Dallos, P. Prestin is the motor protein of cochlear outer hair cells. Nature 2000;405:149–55Google Scholar
84Liberman, MC, Gao, J, He, DZ, Wu, X, Jia, S, Zuo, J. Prestin is required for electromotility of the outer hair cell and for the cochlear amplifier. Nature 2002;419:300–4CrossRefGoogle ScholarPubMed
85Liu, XZ, Ouyang, XM, Xia, XJ, Zheng, J, Pandya, A, Li, F et al. Prestin, a cochlear motor protein, is defective in non-syndromic hearing loss. Hum Mol Genet 2003;12:1155–62Google Scholar
86Brown, SD, Hardisty-Hughes, RE, Mburu, P. Quiet as a mouse: dissecting the molecular and genetic basis of hearing. Nat Rev Genet 2008;9:277–90Google Scholar
87Hardisty-Hughes, RE, Parker, A, Brown, SD. A hearing and vestibular phenotyping pipeline to identify mouse mutants with hearing impairment. Nat Protoc 2010;5:177–90Google Scholar